Pathogen protein modularity enables elaborate mimicry of a host phosphatase
Pathogen protein modularity enables elaborate mimicry of a host phosphatase
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DOI：
10.1016/j.cell.2023.05.049
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发表时间：
2023-06
期刊：
影响因子：
64.5
通讯作者：
Hui Li;Jinlong Wang;T. Kuan;Bozeng Tang;Li Feng;Jiuyu Wang;Zhi Cheng;J. Skłenar;P. Derbyshire;Michelle T. Hulin;Yufei Li;Yi Zhai;Yingnan Hou;Frank L. H. Menke;Yanli Wang;Wenbo Ma
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文献类型：
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作者：
Hui Li;Jinlong Wang;T. Kuan;Bozeng Tang;Li Feng;Jiuyu Wang;Zhi Cheng;J. Skłenar;P. Derbyshire;Michelle T. Hulin;Yufei Li;Yi Zhai;Yingnan Hou;Frank L. H. Menke;Yanli Wang;Wenbo Ma
病原体产生不同的效应蛋白来操纵宿主细胞过程。然而，功能多样性是如何产生的效应库知之甚少。在植物病原菌中，许多效应子都含有“（L）WY”基序的串联重复序列，这些基序结构保守，但序列可变。在此，我们发现了一个由多个植物受体中的特异性（L）WY-LWY组合形成的功能模块，该功能模块有效地在植物宿主中募集丝氨酸/苏氨酸蛋白磷酸酶2A（PP 2A）核心酶。效应子-PP 2A复合物的晶体结构显示（L）WY-LWY模块能够劫持宿主PP 2A核心酶以形成功能性全酶。虽然在氨基末端共享PP 2A相互作用模块，但这些效应器具有不同的C-末端LWY单位，并调节宿主中不同的磷蛋白组。我们的研究结果强调了一个重要的主机磷酸酶通过分子模拟病原体和多样化的蛋白质模块化促进效应库的拨款。
Pathogens produce diverse effector proteins to manipulate host cellular processes. However, how functional diversity is generated in an effector repertoire is poorly understood. Many effectors in the devastating plant pathogenPhytophthoracontain tandem repeats of the "(L)WY" motif, which are structurally conserved but variable in sequences. Here, we discovered a functional module formed by a specific (L)WY-LWY combination in multiplePhytophthoraeffectors, which efficiently recruits the serine/threonine protein phosphatase 2A (PP2A) core enzyme in plant hosts. Crystal structure of an effector-PP2A complex shows that the (L)WY-LWY module enables hijacking of the host PP2A core enzyme to form functional holoenzymes. While sharing the PP2A-interacting module at the amino terminus, these effectors possess divergent C-terminal LWY units and regulate distinct sets of phosphoproteins in the host. Our results highlight the appropriation of an essential host phosphatase through molecular mimicry by pathogens and diversification promoted by protein modularity in an effector repertoire.